Thienamycin (1) is a recently discovered β-lactam antibiotic of unique structure and exceptional breadth of antibacterial activity, with particular potency against Pseudomonas spp. and β-lactamase stability. However, its chemical instability—including concentration-dependent instability postulated to result from intermolecular aminolysis of the azetidinone by the cysteamine side chain—limits its use as a parenterally administered drug. To address this, we aimed to derivatize the amino group to a less nucleophilic, stronger basic species (existing more in protonated form) to enhance concentrated solution stability and retain high antipseudomonal activity, while also seeking a crystalline derivative for easier purification. We report that N-acetimidoyl (3) and particularly N-formimidoyl (2) derivatives met these goals. The amidines were prepared by reacting thienamycin with imidate esters in aqueous solution at pH 8.2, followed by Dowex 50 X 4 resin chromatography. The crystalline N-formimidoyl derivative showed <1%/h decomposition at 10 mg/mL (projected parenteral concentration) and improved shelf life. Both amidines retained thienamycin’s antibacterial spectrum and exhibited enhanced activity against Pseudomonas aeruginosa. Due to its improved stability and enhanced antipseudomonal activity, N-formimidoylthienamycin (2) was selected for clinical studies.